prophylactic anti-fungal therapy

Nothingcompares

what is it?

DrIndy

prophylactic means to prevent - so you are taking treatment to prevent a fungal infection

Nothingcompares

I could infer that myself but I'm just wondering what kind of treatment is it? Surely just not any kind of preventative measures against fungal infection.

I'm taking it from this context

If you are one of the small percentage of women who suffer from antibiotic induced candidiasis, your doctor may prescribe prophylactic anti-fungal therapy along with the antibiotics.

from http://www.vhi.ie/hfiles/hf-040.jsp

DrIndy

you see it depends on what you are prophylactically treating...... There is more than one type of fungal infection.......

In what context do you mean?

Nothingcompares

Candida

r3nu4l

Candida,

You will usually be prescribed a low dose azole-anti-fungal, this may be clotrimazole as used in Canesten, either in oral tablet, suppositry or cream formulations.

Other such azoles include, econazole, voriconazole, itraconazole, fluconazole, ketoconazole... there are lots of them

Some are more effective than others at killing yeast in different body locations and again it depends on the formulation used. Oral and IV are usually taken for oral and systemic Candida infections whereas the others are usually given for vaginal infection.

These drugs work by inhibiting the formation of sterols that are necessary for the yeast to survive and grow! The act on different parts of the ergosterol synthesis pathway. Side-effects are usually very mild for anti-Candida vaginal treatments. You should ask your GP for more info if you are interested.

I did my PhD on anti-fungal drug-resistance in Candida albicans, Candida dubliniesnsis and Saccharomyces cerevisiae...happy days

tallaght01

r3nu4l wrote:

Candida,

You will usually be prescribed a low dose azole-anti-fungal, this may be clotrimazole as used in Canesten, either in oral tablet, suppositry or cream formulations.

Other such azoles include, econazole, voriconazole, itraconazole, fluconazole, ketoconazole... there are lots of them

Some are more effective than others at killing yeast in different body locations and again it depends on the formulation used. Oral and IV are usually taken for oral and systemic Candida infections whereas the others are usually given for vaginal infection.

These drugs work by inhibiting the formation of sterols that are necessary for the yeast to survive and grow! The act on different parts of the ergosterol synthesis pathway. Side-effects are usually very mild for anti-Candida vaginal treatments. You should ask your GP for more info if you are interested.

I did my PhD on anti-fungal drug-resistance in Candida albicans, Candida dubliniesnsis and Saccharomyces cerevisiae...happy days

Has candida dubliniesnis got any links to Dublin?? You know how some bugs are named after places where they were first classified or whatever

r3nu4l

tallaght01 wrote:

Has candida dubliniesnis got any links to Dublin?? You know how some bugs are named after places where they were first classified or whatever

Yep, the microbiology research lab in the Dental Hospital TCD discovered it Professor David Coleman, Dr Derek Sullivan and Dr Gary Moran were the main investigative team.

They published in Microbiology...it was a race between them and a team in Argentina at teh time

tallaght01

well thank god the Dublin team won, coz candida buenosairesiesnis would have been a total mouthful :P

r3nu4l

Yes it would be:D

To be honest, I worked in that lab for 9 months of my PhD and those guys are very good, innovative thinkers. Hats off to them, very nice guys!

GuanYin

There is a ton of work on this.

Chitosan is a mucoadhesive natural polymer that many groups are trying to direct as an anti-fungal prophylactic therapy.

There is a company in Ireland, Westgate Biological, that was developing compounds in this area, based on whey proteins I believe - they had one toothpaste mentioned in New Scientist.

Other methods we'd commonly use in Gastro is probiotics, although the literature is somewhat split on how effective this actually is long term.

r3nu4l

psi wrote:

There is a ton of work on this.

Chitosan is a mucoadhesive natural polymer that many groups are trying to direct as an anti-fungal prophylactic therapy.

There is a company in Ireland, Westgate Biological, that was developing compounds in this area, based on whey proteins I believe - they had one toothpaste mentioned in New Scientist.

Other methods we'd commonly use in Gastro is probiotics, although the literature is somewhat split on how effective this actually is long term.

Tons of ongoing research but tbh in the GP surgery right now prophylactic therapy refers to azoles. I'm actually attending an expert panel meeting on Canesten later this month! It will be intersting to hear what current opinion is...

Interestingly, for systemic fungal disease there are some hospitals that prescribe oral itraconazole with Cola beverages...the co-administration of flavourings and acid has the double effect of making the drug more palatable and increases bioavailability, respectively!

GuanYin

r3nu4l wrote:

Tons of ongoing research

I have at least two publications in the area

I think the most interesting work was by Alverdy's group in Chicago. They used PEG as an artificial mucin and reduced mortality in intestinally compromised mice by over 90%.

Odd thing is, in my experience, PEG isn't that antimicrobial. The MICs and MBCs I saw were too large, probably because it's almost totally inert. Although he may have used a quaternised version, I don't remember. PEG is fairly well established as being biocompatible so if someone did manage to move it into human trials it would move quite quickly through FDA.

The only one I can think of that is actually through clinical trials is Tolvamer sodium, which is directed against C. diff toxins. Genzyme have that one (I believe they procured it after taking over a Cambridge company called Geltex).

Interestingly, for systemic fungal disease there are some hospitals that prescribe oral itraconazole with Cola beverages...the co-administration of flavourings and acid has the double effect of making the drug more palatable and increases bioavailability, respectively!

well really the way to go with prophylactics is non absorbed cationic molecules imho. I was working on a trial in Dublin to that effect. Was reasonably successful (although as a few boardsies will tell you, the amount of moaning I did about it would make you think otherwise).

tallaght01

In our neonatal unit we have suddenly started putting all the kids on antifungals if they are on more than 2 IV antibiotics. I'm not aware of the evidence for this. I also know of one other unit who's starting the practise locally. Might just be local policy here, but would be curious to know if any of you guys are doing the same with your big people/little people? And are any of you seeing noticeably lower levels of fungal sepsis because of it? I know it's more of an issue in neonates because of their relative immunosuppression and the number of potential infection sources, but was just curious.

DrIndy

is this in the case of sepsis without obvious source? Or is this practise even if the organism in question has been identified?

I would strongly consider antifungal therapy early on in a neutropenic patient. In ICU, it is at times used with antibiotics for sever sepsis.

The trouble is apart from the azoles (which have a much milder side effect profile, but still significant) - the other antifungals have significant toxic side effect profile - notably amphotericin, even the liposomal version.

r3nu4l

As well as the side-effects of AmpB there is also the prohibiive cost of liposomal AmpB but isn't it only a last resort? Hardly for use prophylactically?

GuanYin

tallaght01 wrote:

In our neonatal unit we have suddenly started putting all the kids on antifungals if they are on more than 2 IV antibiotics. I'm not aware of the evidence for this.

Ermm, broad spectrum antibiotics kill off the intestinal commensal microflora, this will leave any young, old, infirm or immunocompromised patient at risk of candidiasis.

It's fairly well established that antifungals should be employed in these cases.

tallaght01

psi wrote:

Ermm, broad spectrum antibiotics kill off the intestinal commensal microflora, this will leave any young, old, infirm or immunocompromised patient at risk of candidiasis.

It's fairly well established that antifungals should be employed in these cases.

Yea, I'm aware of the reasoning behind it. But it's never happened in other baby units where I work. And it never happened in the adult medicine units where I worked (including geriatrics). I was also wondering what the evidence was for it.

DrIndy

ideally, you should try to clear off the candida colonisation with something topical or swallowed, but not absorbed to reduce the need for systemic administration.

tallaght01

is that what happens though? I just don't remember everyone who got onto 2 different IV antibiotics getting an antifungal when i was doing adult medicine.
Candida sepsis is catastrophic in peterm neonates, so it may be just that we have to be more cautious though.

DrIndy

its pretty catastrophic with everyone especially if it isn't the lovely old albicans that can be treated with not so toxic fluconazole - otherwise its zipping them all up on amphotericin and caspofungin and watching their renal and liver function respectively like a hawk.....

GuanYin

DrIndy wrote:

its pretty catastrophic with everyone especially if it isn't the lovely old albicans that can be treated with not so toxic fluconazole - otherwise its zipping them all up on amphotericin and caspofungin and watching their renal and liver function respectively like a hawk.....

Yup, I've only seen it a few times, usually as a complication but it can be disasterous, especially with the immunosuppressed or, the worst case I recall, during pregnancy.

r3nu4l

Hi guys, I was away with work for a while so haven't responded to this thread. I have a question about prophylactic use in the clinical setting.

Are allylamines such as terbinafine ever prescribed prophylactically or are they considered too narrow in spectrum?

/EDIT I had a second question but tbh it could be construed as 'market research' thanks to a conflict of interest at my workplace so I won't ask it here.

I have a strong interest in anti-fungal therapy thanks to my PhD but Bayer are one of my clients and I work on the Canesten account amongst others so it wouldn't be right of me to ask...

tallaght01

It's always fluconazole in my neck of the woods.

r3nu4l

tallaght01 wrote:

It's always fluconazole in my neck of the woods.

Yeah, from what I've heard fluconazole seems to be the 'gold standard' of azoles. If you don't want to use AmpB then fluconazole sems to be the standard choice!

tallaght01

we are indeed fluconazole crazy. Having said that, I still haven't bothered to look up the literature to see if there's any good evidence for the way we use it as soon as the kiddie hits their 2nd IV antibiotic.
we also like ambisome For treatment, rather than prophylaxis). variety is the spice of life and all that :P

r3nu4l

tallaght01 wrote:

we also like ambisome For treatment, rather than prophylaxis). variety is the spice of life and all that :P

In neoatal kids!! :eek: That's seriously expensive and must still be hepatotoxic to neonates despite the liposomal formulation given that these kids are just out of the womb?

Fluconazole I understand but ambisome? The infection must be at a life or death stage before using it, yeah?

tallaght01

r3nu4l wrote:

In neoatal kids!! :eek: That's seriously expensive and must still be hepatotoxic to neonates despite the liposomal formulation given that these kids are just out of the womb?

Fluconazole I understand but ambisome? The infection must be at a life or death stage before using it, yeah?

Yep, but most fungal sepsis is life or death in neonates. Ambisome has a broader spectrum of coverage than fluconazole too, as I'm sure you know. A surprising amount of our kiddies end up on it. Get a lot of hepatotoxicity (as measured by their LFTs), but it's usually reversible. That's the official line anyway. I'm firmly of the belief that we use it because we just want to show off that we have more money than the rest of the units in the hospital :P

DrIndy

fluconazole will only guarrantee effectiveness with candida albicans, the other species have resistance to it, hence all you have available to you is ambisome.

tallaght01

yea but if fluconazole doesn't do the job on candida sepsis, then ambisome nearly always will.might knock the bolix outa your liver, but it'll mop up the fungus good style